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Home/Research/Psilocybin/Personality Disorders

Psilocybin for Personality Disorders

5 papers and 1 clinical trial exploring psilocybin as a treatment for personality disorders.

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

Full Psilocybin profile
IndicationApproximately 9% of adults globally.

Personality Disorders

Personality disorders, characterised by enduring patterns of behaviour, cognition, and inner experience, present substantial challenges in treatment. Emerging research into psychedelics such as psilocybin, MDMA, and ketamine indicates that they may offer novel therapeutic avenues for addressing these complex conditions.

Full Personality Disorders profile

Academic Research

5 papers
Paywallindividual

An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder

This open-label pilot study (n=9) tested a single dose of psilocybin in adults with borderline personality disorder and major depressive disorder. Depressive symptoms improved over four weeks, but borderline personality disorder symptoms did not change significantly.

Published
April 1, 2026
Journal
Journal of Clinical Psychopharmacology
Authors
Grant, J. E., Boutouis, S., O’Brien, M., Avila, L., Neelapu, M., Ehsan, D.
Paywallindividual

The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis

In a retrospective analysis of 233 participants with treatment‑resistant depression given 1, 10 or 25 mg COMP360 psilocybin, dose was the strongest and most consistent predictor of the acute psychedelic experience, while pretreatment clinical characteristics made only modest, variable contributions (positive affect, lower generalized anxiety, higher executive function and greater personality‑disorder symptoms each influenced different experience dimensions). These results challenge the assumption that pretreatment traits are major determinants of the subjective psilocybin experience.

Published
December 9, 2025
Journal
Journal of Clinical Psychopharmacology
Authors
Kirlić, N., Atli, M., Mistry, S., Gold, M., Goodwin, G. M.
Paywallindividual

Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin

This open-label waitlist trial (n=30) assessed the feasibility of psilocybin-assisted psychotherapy (PAP/PAT) in a complex population with treatment-resistant depression (TRD), including major depressive and bipolar II disorders, baseline suicidality, and significant comorbidity. Participants received one, two, or three sessions of PAP with psilocybin (25mg), accompanied by preparation and integration psychotherapy sessions. Immediate treatment showed greater reductions in depression severity (MADRS) compared to the waitlist period, with a large effect size (g = 1.07, p < 0.01). Repeated doses were associated with further reductions in depression severity. Adverse events were transient, and the study demonstrated feasibility, preliminary antidepressant efficacy, safety, and tolerability in this population.

Published
March 1, 2024
Journal
Med
Authors
Rosenblat, J. D., Meshkat, S., Doyle, Z., Zumrova, A., Marlborough, M., Mcintyre, R. S., Kaczmarek, E., Brudner, R. M., Kratiuk, K., Mansur, R. B., Schulz-Quach, C., Sethi, R., Abate, A., Ali, S., Bawks, J., Blainey, M. G., Brietzke, E., Cronin, V., Danilewitz, J., Dhawan, S., Fonzo, A. D., Fonzo, M. D., Drzadzewski, P., Dunlop, W., Fiszter, H., Gomes, F. A., Grewal, S., Leon-Carlyle, M., Mccallum, M., Mofidi, N., Offman, H., Riva-Cambrin, J., Schmidt, J., Smolkin, M., Quinn, J. M.
Open Accessindividual

Effect of psilocybin on empathy and moral decision-making

This placebo-controlled study (n=56) investigated the acute effect of psilocybin (15mg/70kg) on empathy and moral decision-making in healthy human subjects. The results found the first such evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. It also supports previous findings, indicating that psilocybin may promote emotional empathy presumably through activation of serotonin 2A/1A receptors, showing that focusing on serotonin 2A/1A receptors has the potential to treat dysfunctional social cognition.

Published
June 16, 2017
Journal
International Journal of Neuropsychopharmacology
Authors
Pokorny, T., Preller, K. H., Kometer, M., Dziobek, I., Vollenweider, F. X.
Open Accessmeta

Ayahuasca: pharmacology, neuroscience and therapeutic potential

This review (2016) examines the pharmacology and neuroscience of ayahuasca, and preliminary findings which indicate the psychological mechanisms associated with its therapeutic benefits are similar to those of mindfulness-based therapy. Ayahuasca appears to enhance self-acceptance and decentering, which converges on evidence from neuroimaging studies that show activation in areas associated with emotional processing and memory formation, thereby enabling individuals to review emotional events with increased vividness and a heightened sense of “reality”. This suggests potential to treat trauma-related conditions and other disorders like borderline personality disorder.

Published
September 1, 2016
Journal
Brain Research Bulletin
Authors
Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J. C., Álvarez, E., De La Fuente Revenga, M., Friedlander, P., Feilding, A., Riba, J.

Clinical Trials

1 trial
CompletedPhase II

Psilocybin in Co-occuring Major Depressive Disorder and Borderline Personality Disorder

Open-label, single-group Phase II study (n=10) assessing a single 25 mg oral dose of psilocybin for adults with MDD and co-occurring BPD to evaluate safety and efficacy.

Started
September 1, 2022
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT05399498

Explore further

Search all Psilocybin papers Search all Personality Disorders trials Full Psilocybin profile Full Personality Disorders profile